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Dosing of selected parenteral beta-lactam antibiotics for adult patients

Dosing of selected parenteral beta-lactam antibiotics for adult patients
Drug CrCl (mL/minute) Adult dose Frequency
Beta-lactamase inhibitor combinations
Ampicillin-sulbactam (mild to moderate infections) ≥30 1.5 g Every 6 hours
15 to 29 1.5 g Every 12 hours
5 to 14 1.5 g Every 24 hours
iHD* 1.5 g Every 12 to 24 hours
CRRT[1] 1.5 g Every 6 to 12 hours
Ampicillin-sulbactam (moderate to severe infections) ≥30 3 g Every 6 hours
15 to 29 3 g Every 12 hours
5 to 14 3 g Every 24 hours
iHD* 3 g Every 12 to 24 hours
CRRT[1] 3 g Every 6 to 12 hours
Ceftazidime-avibactam >50 2.5 g Every 8 hours
31 to 50 1.25 g Every 8 hours
16 to 30 0.94 g Every 12 hours
6 to 15 0.94 g Every 24 hours
≤5 0.94 g Every 48 hours
iHD* 0.94 g

CrCl 6 to 15 mL/minute: Every 24 hours

CrCl ≤5 mL/minute: Every 48 hours

Administer after iHD on dialysis days
CRRT[2] (based on preliminary data) 1.25 g Every 8 hours
Ceftolozane-tazobactam (complicated UTI and intra-abdominal infections) >50 1.5 g Every 8 hours
30 to 50 750 mg Every 8 hours
15 to 29 375 mg Every 8 hours
<15 Has not been studied  
iHD* 750 mg once, followed by 150 mg Every 8 hours
CRRT[3] (based on preliminary data) 750 mg Every 8 hours
Ceftolozane-tazobactam (severe infections)[4,5] >50 3 g Every 8 hours
30 to 50 1.5 g Every 8 hours
15 to 29 750 mg Every 8 hours
<15 Has not been studied  
iHD* 750 mg once, followed by 375 mg Every 8 hours
CRRT[3] (based on preliminary data) 1.5 g Every 8 hours
Imipenem-cilastatin-relebactam ≥90 1.25 g Every 6 hours
60 to 89 1 g Every 6 hours
30 to 59 0.75 g Every 6 hours
15 to 29 0.5 g Every 6 hours
iHD* 0.5 g Every 6 hours; administer after iHD on dialysis days

Meropenem-vaborbactam

NOTE: Use MDRD equation formula to estimate renal function (eGFR) 		≥50 4 g Every 8 hours (infused over 3 hours)
30 to 49 2 g Every 8 hours (infused over 3 hours)
15 to 29 2 g Every 12 hours (infused over 3 hours)
<15 1 g Every 12 hours (infused over 3 hours)
iHD* 1 g Every 12 hours (infused over 3 hours) administered after an iHD session
Piperacillin-tazobactam (mild to moderate infections) >40 3.375 g Every 6 hours
20 to 40 2.25 g Every 6 hours
<20 2.25 g Every 8 hours
iHD* 2.25 g Every 12 hours
CRRT[1] 2.25 g Every 6 to 8 hours
Piperacillin-tazobactam (severe infections, including Pseudomonas aeruginosa) >40 4.5 g Every 6 hours
20 to 40 3.375 g Every 6 hours
<20 2.25 g Every 6 hours
iHD* 2.25 g Every 8 hours
CRRT[1] 3.375 g Every 6 to 8 hours
Carbapenems
Doripenem >50 500 mg Every 8 hours
30 to 50 250 mg Every 8 hours
11 to 29 250 mg Every 12 hours
<10 Has not been studied  
iHD* 250 to 500 mg Every 24 hours
CRRT 250 mg to 1 g Every 8 to 12 hours
Ertapenem >30 1 g Every 24 hours
≤30 500 mg Every 24 hours
iHD* 500 mg Every 24 hours; administer after iHD on dialysis days
CRRT[6] (based on preliminary data) 1 g Every 24 hours
Imipenem-cilastatin (moderate infection)[7] >70 to 89 500 mg Every 6 hours
41 to 70 500 mg Every 8 hours
21 to 40 250 mg Every 6 hours
<21 250 mg Every 12 hours
iHD* 250 mg Every 12 hours; administer after iHD on dialysis days
CRRT[1] 250 to 500 mg Every 6 to 8 hours
Imipenem-cilastatin (severe infection)[7] >70 to 89 1 g Every 6Δ to 8 hours
41 to 70 500 mg Every 6 hours
21 to 40 500 mg Every 8 hours
<21 500 mg Every 12 hours
iHD* 500 mg Every 12 hours; administer after iHD on dialysis days
CRRT[1] 500 mg Every 6 to 8 hours
Meropenem (meningitis, cystic fibrosis pulmonary exacerbation) >50 2 g Every 8 hours
26 to 50 2 g Every 12 hours
10 to 25 1 g Every 12 hours
<10 1 g Every 24 hours
iHD* 1 g Every 24 hours; administer after iHD on dialysis days
CRRT[1] 500 mg or 1 g Every 8 to 12 hours
Meropenem (moderate to severe infection)◊ >50 1 g Every 8 hours
26 to 50 1 g Every 12 hours
10 to 25 500 mg Every 12 hours
<10 500 mg Every 24 hours
iHD* 500 mg Every 24 hours; administer after iHD on dialysis days
CRRT[1] 500 mg or 1 g Every 8 to 12 hours
Monobactam
Aztreonam (moderate infection) >30 1 g Every 8 hours
10 to 30 500 mg Every 8 hours
<10 250 mg Every 8 hours
iHD* 1 g once, followed by 250 mg Every 8 to 12 hours
CRRT[1] 2 g once, followed by 1 or 2 g 1 g every 8 hours or 1 to 2 g every 12 hours
Aztreonam (severe infection) >30 2 g Every 8 hours
10 to 30 1 g Every 8 hours
<10 500 mg Every 8 hours
iHD* 2 g once, followed by 500 mg Every 8 hours
CRRT[1] 2 g once, followed by 1 or 2 g 1 g every 8 hours or 1 to 2 g every 12 hours
This table lists doses of selected beta-lactam antibiotics, with suggested dosing adjustments for renal impairment. The first dose listed for each agent represents the suggested dose for normal renal function. Renal function is evaluated based on estimated CrCl using the Cockcroft-Gault equation. A calculator for estimating CrCl based on the Cockcroft-Gault equation is available in UpToDate.
NOTE: Doses listed for the combination beta-lactam/beta-lactamase inhibitors are expressed as the total of grams for both components.
CrCl: creatinine clearance; iHD: intermittent hemodialysis; CRRT: continuous renal replacement therapy; MDRD: Modification of Diet in Renal Disease; eGFR: estimated glomerular filtration rate.
* Based on three times weekly dialysis sessions of 3 to 4 hours each; on dialysis days administer dose after dialysis. A loading dose may be warranted for some antibiotics depending on clinical scenario; refer to Lexicomp monograph for detail.
¶ General dose and interval range for different types of CRRT based on dialysate/ultrafiltration rate of 1 to 2 L/hour are listed. Specific dosing depends on CRRT method, flow rate, and filter type. For specific recommendations; refer to Lexicomp monograph included in UpToDate.
Δ An imipenem dose of 1 g given every 6 hours has been associated with an increased risk of seizures.[8]
◊ A lower dose is recommended for some skin/skin structure and urinary tract infections. Refer to Lexicomp monograph.
References:
  1. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy 2009; 29:562.
  2. Wenzler E, Bunnel KL, Belasdale SC, et al. Pharmacokinetics and dialytic clearance of ceftazidime-avibactam in a critically ill patient on continuous venovenous hemofiltration. Antimicrobial Agents Chemother 2017 [Epub ahead of print].
  3. Bremmer DN, Nicolau DP, Burcham P, et al. Ceftolozane/tazobactam pharmacokinetics in a critically ill adult receiving continuous renal replacement therapy. Pharmacotherapy 2016; 36:e30.
  4. Munita JM, Aitken SL, Miller WR, et al. Multicenter evaluation of ceftolozane/tazobactam for serious infections caused by carbapenem-resistant Pseudomonas aeruginosa. Clin Infect Dis 2017 [Epub ahead of print].
  5. Caston JJ, De la Torre A, Ruiz Camps I, et al. Salvage therapy with ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections. Antimicrob Agents Chemother 2017; 61:e02136.
  6. Eyler RF, Vilay AM, Nader AM, et al. Pharmacokinetics of ertapenem in critically ill patients receiving continuous venovenous hemodialysis or hemodiafiltration. Antimicrob Agents Chemother 2014; 58:1320.
  7. Pham PA, Bartlett JG. Imipenem/cilastatin. In: Johns Hopkins Antibiotics Guide (https://www.hopkinsguides.com/hopkins), Unbound Medicine, 2017.
  8. Zhanel GG, Wiebe R, Dilay L, et al. Comparative review of the carbapenems. Drugs 2007; 67:1027.
Courtesy of Stephen B Calderwood, MD and Alyssa R Letourneau, MD, with additional data from Lexicomp Online. Copyright © 1978-2023 Lexicomp, Inc. All Rights Reserved.
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